Myo-Inositol and phosphoinositides are important membrane components which appear to be involved in several fundamental physiological processes including secretion of hormones and synaptic transmission and axonal conduction. Preliminary studies have studies have shown that lithium produces marked alterations in the levels of myo-inositol and myo-inositol l-phosphate in tissues and these effects in brain have been found to be inhibited by anticholinergic agents. The objectives of the proposed research are to obtain a comprehensive picture of the lithium-induced in the metabolism of this biochemical system and to determine the mechanisms underlying the alterations produced by lithium and the inhibition produced by the anticholinergc drugs. This will be carried out by studying the effects of lithium on the levels of myo-inositol, myo-inositol phosphates and phosphoinositides in brain and selected peripheral organs following acute and chronic administration of the drug and by examination of the effects of lithium and atropine on the transport and synthesis of myo-inositol and of lithium on the synthesis of phosphoinositides by studying the uptake and incorporation of radioactively labelled precursors. Also studies will be performed to determine drugs which are known to stimulate cholinergic transmission such as pilocarpine and physostigmine produce the same pattern of metabolic changes as found with lithium. The primary analytical methods to be used include gas chromatography, mass spectrometry and quantitative histochemistry. The results of this project will contribute to our knowledge of the effects of lithium on biochemical processes related to membrane function and will provide evidence regarding the usefulness of lithium as a pharmacological tool in further studies of the functional role of my-inositol and the phosphoinositides.